SARS-CoV-2 and other viruses
“The development of Space was followed by mutant viruses and a global pandemic”
― Steven Magee
Macrodomains in viral infection
In response to the emergence of the SARS-CoV-2 virus at the beginning of 2020 and the following pandemic a lot of research effort was devoted to the main druggable targets of the virus, including the SARS-CoV-2 macro domain Mac1.
Macro domains can be found in multiple organisms and facilitate the addition and removal of ADP-ribose, a post-translational protein modification that is crucial for many biological processes. In fact, certain macro domains in several alpha viruses as well as in SARS-CoV-2 are responsible for reversing mono-ADP-ribosylation, which is initially introduced as a defensive mechanism by human ADP-ribosyltransferases. Thus, inactivation or inhibition of viral macro domains reduces pathogenicity in interferon-proficient cells.
In collaboration with our partners from the Volkswagenstiftung we plan to address the demand for inhibitors of viral macro domains and are currently working on the design of small molecules that selectively target the SARS-CoV-2 macro domain Mac1.
People involved
Verena Weber
Ph.D. student
Prof. Dr. Giulia Rossetti
Group leader of Drug Design Hub for Digital Neuropharmacology
Collaborators
- Prof. Bernhard Lüscher (RWTH Aachen)
- Dr. Patricia Korn (RWTH Aachen)
- Prof. Andreas Ladurner (LMU Munich)
- Prof. Stefan Knapp (Goethe University Frankfurt)
Fundings
Mpro
Among the many different strategies to tackle an ongoing SARS-CoV-2 infection, the inhibition of the virus’ main protease (Mpro or 3CLPro) and the disruption of its surface protein Spike adhesion to human cells are the most studied.
We aim to further characterize the chemical features of the bindings site of these proteins to accelerate and direct the discovery of new inhibitors.
People involved
Verena Weber
Ph.D. student
Prof. Dr. Giulia Rossetti
Group leader of Drug Design Hub for Digital Neuropharmacology
Collaborators
- Dr. Antonella Di Pizio (Technischen Universität München)
- Dr. Paola Storici (Elettra Sincrotrone Trieste, ITALY)
- Prof. Francesca Spyrakis (University of Turin, ITALY)
- Prof. Dr. Rebecca Wade (Heidelberg Institute for Theoretical Studies)
- Dr. Andrea Zaliani (Frauenhofer-Institut für Molekularbiologie und Angewandte Ökologie, Hamburg)